In recent years, attention is drawn to the accumulation of sorbitol in cells via a polyol pathway, i.e. a metabolic pathway of glucose, as a causative factor of various of a complication in diabetes of cataract, retinopathy, keratopathy, nephrosis, and neuropathy. This polyol pathway is the metabolic pathway of converting aldoses e.g. glucose, galactose, etc., through polyols e.g. sorbitol, galactitol, etc., into ketoses e.g. fructose, etc. According to immunotissue-chemical techniques, this pathway was proved to occur widely in various tissues.
The enzyme catalyzing conversion between aldoses and polyols (i.e. the first step of this pathway) is called aldose reductase, and this enzyme is considered the rate-limiting enzyme in the polyol pathway. It has been reported that various complications in patients with diabetes are effectively prevented and cured by inhibiting of aldose reductase and lowering the production and accumulation of sorbitol (Pharmacia, 24:459 (1988)).
Under the circumstances, it has been desired to develop pharmaceuticals with the inhibitory action on aldose reductase.
As pharmaceuticals with the inhibitory action on aldose reductase, Japanese Patent Appln. LOP Publication No. 228914/1989 discloses chromone derivatives, Capillarisin (R=H) and 7-methyl Capillarisin (R= CH.sub.3), which having been isolated from the herb of Artemisia capillaris thunb and are represented by Formula: ##STR2## Among prior art compounds similar in structure to Capillarisin, chromone derivatives, which are represented by Formula (A): ##STR3## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are set forth in Table 2, belong to the prior art (for example, Japanese Patent Appln. LOP Publications Nos. 169586/1990, and 39085/1981 and Journal of the Pharmaceutical Society of Japan, 96:841(1976) and 96:855 (1976)). However, no reports have revealed whether the chromone derivatives exhibit the inhibitory action on aldose reductase.
TABLE 2 ______________________________________ R.sub.1 R.sub.2 R.sub.3 R.sub.4 R.sub.5 R.sub.6 ______________________________________ CH.sub.3 H O OCH.sub.3 H H CH.sub.3 H O OCH.sub.3 CH.sub.3 H CH.sub.3 CH.sub.3 O OCH.sub.3 CH.sub.3 H C.sub.2 H.sub.5 H O OCH.sub.3 C.sub.2 H.sub.5 H C.sub.2 H.sub.5 C.sub.2 H.sub.5 O OCH.sub.3 C.sub.2 H.sub.5 H COCH.sub.3 COCH.sub.3 O OCH.sub.3 COCH.sub.3 H H H S OCH.sub.3 H H H CH.sub.3 O H H H CH.sub.3 CH.sub.3 O H CH.sub.3 H CH.sub.3 H O H H H H H O H H H H H O H CH.sub.3 H CH.sub.3 H O H CH.sub.3 H ______________________________________